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A solution of 8-methyl-8-azabicyclo[3.2.1]octan-3-one (2.79 g, 20 mmol) in anhydrous tetrahydrofuran (40 mL) under nitrogen was cooled (-68° C.) and treated (via syringe) with 1.0N lithium bis(trimethylsilyl)amide/tetrahydrofuran (36 mL, 36 mmol) at a rate to keep the pot temperature below -55° C. The mixture was warmed to 0° C., then recooled (-68° C.), and treated dropwise with a solution of n-butyl nitrite (2.6 mL, 22 mmol) in anhydrous tetrahydrofuran (15 mL) at a rate to keep the pot temperature below -60° C. The mixture was warmed to room temperature over one h, stirred for one h, and quenched with saturated ammonium chloride (15 mL). The organic layer was separated and the aqueous solution was extracted with toluene (50 mL) containing some 2-propanol. The combined organic solution was dried (Na2SO4) and concentrated in vacuo. The residue was chromatographed on silica gel (eluted with 9:1 ethyl acetate/methanol, then with 3:2 ethyl acetate/methanol) to afford, first, 8-methyl-8-azabicyclo[3.2.1]octane-2,3-dione-2-oxime (0.43 g, 13%, beige solid), then recovered starting material (1.40 g). Product yield was 26% based on recovered starting material.

1. customthe pot temperature below -55° C
2. custom(-68° C.)
3. customthe pot temperature below -60° C
4. temperatureThe mixture was warmed to room temperature over one h
5. customquenched with saturated ammonium chloride (15 mL)
6. customThe organic layer was separated
7. extractionthe aqueous solution was extracted with toluene (50 mL)
8. additioncontaining some 2-propanol
9. dry with materialThe combined organic solution was dried (Na2SO4)
10. concentrationconcentrated in vacuo
11. customThe residue was chromatographed on silica gel (
12. washeluted with 9:1 ethyl acetate/methanol
13. customwith 3:2 ethyl acetate/methanol) to afford
14. customfirst, 8-methyl-8-azabicyclo[3.2.1]octane-2,3-dione-2-oxime (0.43 g, 13%, beige solid), then recovered